AAP Lead Testing Webinar Series

Transcription

1 AAP Lead Testing Webinar Series This event is the first of a 4-part webinar series developed as part of the American Academy of Pediatrics (AAP) project, Increasing Capacity for Blood Lead Testing and Interpretive Guidance for Blood Lead Results. The webinar materials are developed and presented by pediatric lead experts from the AAP to educate primary care providers on various aspects of lead exposure prevention, testing, treatment, and follow up care.

2 DISCLAIMER This webinar was supported by the Cooperative Agreement Number, NU38OT000282, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the American Academy of Pediatrics, Centers for Disease Control and Prevention or the Department of Health and Human Services.

3 Understanding CDC's Blood Lead Reference Value: Laboratory Best Practices & How To Interpret Results Jennifer A. Lowry, MD, FAAP Director, Pediatric Environmental Health Specialty Unit Region 7 PEHSU Director, Division of Pharmacology, Toxicology and Therapeutic Innovation, Children s Mercy Kansas City Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

4 OBJECTIVES 1. Understand what the reference level means to the actions taken in children with elevated blood lead levels 2. Describe laboratory tests used to evaluate blood lead levels 3. Discuss limitations of various methods of blood lead testing and how it impacts decision making in pediatric practices

5 Reference Value

6 REFERENCE VALUE Source: National Health and Nutrition Examination Survey (NHANES)

7 CDC REFERENCE VALUE: WHAT DOES IT MEAN?? It is a number based on a nationally representative population of children between 1-5 years of age who had lead levels done and 97.5% of children were below that number. It does NOT indicate lead poisoning or toxicity. It is just a reference point based on population data. It is NOT indicative of what the clinical laboratory can tell you about the individual child in your practice.

8 RECOMMENDED ACTIONS TAKEN AT REFERENCE VALUE Source: Centers for Disease Control and Prevention (CDC); National Center for Environmental Health (NCEH)/Lead

9 RECOMMENDED ACTIONS TAKEN AT REFERENCE VALUE Source:

10 RECOMMENDED ACTIONS TAKEN AT REFERENCE VALUE Environmental investigations at BLLs 5 19 μg/dl vary according to local conditions based on jurisdictional requirements and available resources Providers must know available resources and how to respond to lead level results

11 Laboratory Test Available to Evaluate Blood Lead Levels

12 COMMONLYUSED AVAILABLEMETHODS Anodic Stripping Voltammetry (ASV) Disposable screen printed electrode technologies (LeadCare II) Graphite furnace atomic absorption spectrometry (GFAAS) Reference method Inductively coupled plasma mass spectrometry (ICP-MS) Reference method

13 Point of Care testing Physician s offices LEADCARE II Local health departments Hospitals CLIA waived Capillary blood samples only Confirmation testing should be venous blood by a different method Reportable range is µg/dl State health department reporting is the same as for lab-based tests

14 SEQUENTIAL BLOOD LEAD MEASUREMENT ON LEADCARE II Simulation of sequential blood lead level measurements for person with constant, true blood lead of 5.0 µg/dl 7 6 Blood lead (µg/dl) Sequential blood lead measurements on LeadCare II Source: National Center for Environmental Health (NCEH)/ATSDR Board of Scientific Counselors, Semi-Annual Meeting, January 2017

15 GRAPHITE FURNACE ATOMIC ABSORPTION SPECTROMETRY Electrical heated graphite coded tubes or rods that vaporize sample Amount of light energy absorbed at frequency characteristic to element Amount of light absorption can be linearly correlated to concentration Source: Courtesy of Patrick Parsons, PhD

16 GRAPHITE FURNACE ATOMIC ABSORPTION SPECTROMETRY Hospital or reference lab settings CLIA: High complexity Capillary or venous samples Can be used for venous confirmation on different blood sample Reportable range: capable of accurately measuring to 1 µg/dl

17 INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY Provides high temperature ion source resulting in all bonds broken irrespective of their chemical bonding Accounts for total content of an element

18 INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY Hospital or reference lab settings CLIA: High complexity Capillary or venous samples Can be used for venous confirmation on different blood sample Reportable range: capable of accurately measuring below 1 µg/dl with better precision compared to GFAAS

19 BEST ESTIMATES OF PRECISION OF BLOOD LEAD MEASUREMENTS AT 5 UG/DL 95% confidence interval (µg/dl) LeadCare II ± GFAAS ± ICP-MS ± N Source: National Center on Environmental Health (NCEH)/ATSDR Board of Scientific Counselors, Semi-Annual Meeting, January 2017

20 Limitations of Laboratory Instruments in Blood Lead Results Based on Reference Value

21 PROCEDURES FOR COLLECTING SAMPLES FOR Capillary blood samples LEAD DETERMINATION Acceptable only for screening purposes False positives can be frequent but inform the provider on environment

22 PROCEDURES FOR COLLECTING SAMPLES FOR LEAD DETERMINATION Filter paper collection Varied opinions on reliability and technique Potential for contamination and variable volume Guidelines for methods of measuring lead from filter paper

23 PROCEDURES FOR COLLECTING SAMPLES FOR LEAD DETERMINATION Instrument precision ICP-MS and GFAAS can be reproducible to µg/dl at low levels Reporting at low levels as clinical value is open to interpretation Quantitation limits Current CLIA regulations within the United States require that the acceptability limits be no larger than ± 4 µg/dl (0.19 µmol/l) below 40 µg/dl (1.93 µmol/l), or ± 10% of the target value above that concentration Repeat testing

24 LABORATORY REPORTING Prior to reporting patient test results, the laboratory must provide performance specifications Accuracy Precision Reportable Range Reference Intervals

25 Accuracy LABORATORY REPORTING Degree of closeness of measurements of a quantity to that quantity s actual value Precision Also called reproducibility or repeatability Same results: Day-to-day Run-to-run Within run Operator variance

26 Reportable range LABORATORY REPORTING Laboratory is responsible for establishing how high and low the results can be reported Based on LOD and LOQ Reference intervals or normal values Must be appropriate for laboratory s patient population May establish own reference range or use published ranges

27 LABORATORY REPORTING Limit of Detection Lowest concentration of analyte that the test can detect or distinguish from a blank Limit of Quantification Lowest quantity that can be accurately measured

28 IMPRECISION INCREASES NON-LINEARLY NEAR THE LIMIT OF DETECTION 2.0 Y 95% confidence interval 1.8 Y 1.6 Y 1.4 Y 1.2 Y Y.8 Y.6 Y.4 Y.2 Y 0 LOD Concentration Adapted from JK Taylor, Quality Assurance of Chemical Measurements, 1987.

29 LABORATORYREFERENCEINTERVAL FOR LEAD Different than CDC Reference Value (different meaning) Based on LOD and LOQ of instrumentation and what can most accurately be reported Current agreement is that precision for measurements made at 3.5 µg/dl will not be better than the current estimates at 5 µg/dl CDC changes in reference value will not change laboratory reference levels until better precision can be made

30 Impact on Patient Care

31 INTERPRETATION OF RESULTS There is no known safe level of blood lead for children Depending on method used, the actual result should be within +2 SD knowing the precision is poorer at lower concentrations. For example, a blood lead level of 4.9 µg/dl from LeadCare II could be in a range of µg/dl (roughly)

32 RECOMMENDATIONS FOR ACTION There is no known safe blood lead level Local and state regulations guide involvement of health department for case management and home assessments (e.g., blood lead level of 4.9 µg/dl) Health care providers must supply education and be involved when the health departments cannot (e.g., blood lead level of 4.9 µg/dl) CDC and Pediatric Environmental Health Specialty Unit (PEHSU) guidance Virtual home assessments Lead questionnaire to help determine source

33 Confirmatory testing ADDITIONAL TESTING Capillary screening would be considered the first test to determine if the child has an elevated blood lead level. If above 5 µg/dl, this should be repeated with a venous sample by a different method. If venous is below LOR, consider lead may still be in environment and education on sources is still needed for primary prevention Repeat testing If child has had EBLL confirmed by venous testing, all further testing should be by venous sampling. Follow testing schedule recommended by CDC and/or PEHSU

34 SUMMARY CDC Lead Reference Value (5 µg/dl) Based on data obtained from a representative population of children in the U.S. This number will change based on the work we do to prevent lead poisoning Laboratory Lead Reference Value (5 µg/dl) Based on precision testing of methods by laboratories to determine accurate results from LOD and LOQ This number may change as precision in methods improves

35 SUMMARY CDC and Laboratory Reference Values may not always be the same. Public health management is based on local and state jurisdictions and availability of resources. They may not be able to provide services at CDC Reference Value. Health care providers should understand limitations of methods for lead quantitation and provide appropriate education to families.

36 Questions? Thank you!